Previous studies under this project and by other investigators have shown acid neuraminidase deficiency to represent the primary defect in mucolipidosis I and two forms of the cherry-red spot myoclonus syndrome. Deficiency of this enzyme represents a secondary biochemical feature of mucolipidosis II and III. The clinical variability of ML I will be further studied by longitudinal evaluations of three children with this disorder and use of screening tests and definitive diagnostic tests to detect additional patients. Urine, cultured fibroblasts and tissue will be analyzed to determine the compounds accummulating in this lysosomal storage disease and a variety of substrates will be used to define the specificity of the deficient neuraminidase. The availability of the fluroscent substrate methyl-umbelliferyl-neuraminic acid will allow for detection of small amounts of enzyme activity thereby permitting analysis of somatic cell hybrids as a means to explore genetic heterogeneity among acid neuraminidase deficient disorders. The role of acid neuraminidase deficiency on the multiple enzyme changes in ML II. especially enzyme uptake by cultured fibroblasts, will be explored using cell lines from ML, I, II, III and "variant mucolipidoses."